PAK1 protein expression in the auditory cortex of schizophrenia subjects.
PAK1 protein expression in the auditory cortex of schizophrenia subjects.
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DOI：
10.1371/journal.pone.0059458
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Sweet RA
中科院分区：
文献类型：
--
作者：
Deo AJ;Goldszer IM;Li S;DiBitetto JV;Henteleff R;Sampson A;Lewis DA;Penzes P;Sweet RA
听觉处理缺陷是精神分裂症中记录最充分的内表型之一，可能是由于兴奋性突触连接的丧失。树突棘，兴奋性投射的主要突触后目标，在精神分裂症中减少。p21活化激酶1 （PAK1）调节肌动蛋白细胞骨架和树突棘密度，是kalirin和CDC42的下游效应物，两者在精神分裂症中表达改变。本研究试图通过对25名精神分裂症患者和匹配对照进行定量western blot，确定精神分裂症患者的听觉皮层PAK1蛋白表达是否降低。在我们的队列中，在精神分裂症受试者中检测到PAK1水平没有显著变化。受试者对中PAK1蛋白水平与同一对中先前测量的总钾素蛋白水平呈正相关。PAK1水平也与树突棘标志物嗜脊髓蛋白水平相关。后两项研究结果表明，精神分裂症患者PAK1水平缺乏变化并不是因为我们检测PAK1蛋白表达差异的灵敏度有限。未来的研究需要评估PAK1磷酸化状态的改变，或PAK1家族其他成员蛋白表达的改变是否存在于精神分裂症中。
Deficits in auditory processing are among the best documented endophenotypes in schizophrenia, possibly due to loss of excitatory synaptic connections. Dendritic spines, the principal post-synaptic target of excitatory projections, are reduced in schizophrenia. p21-activated kinase 1 (PAK1) regulates both the actin cytoskeleton and dendritic spine density, and is a downstream effector of both kalirin and CDC42, both of which have altered expression in schizophrenia. This study sought to determine if there is decreased auditory cortex PAK1 protein expression in schizophrenia through the use of quantitative western blots of 25 schizophrenia subjects and matched controls. There was no significant change in PAK1 level detected in the schizophrenia subjects in our cohort. PAK1 protein levels within subject pairs correlated positively with prior measures of total kalirin protein in the same pairs. PAK1 level also correlated with levels of a marker of dendritic spines, spinophilin. These latter two findings suggest that the lack of change in PAK1 level in schizophrenia is not due to limited sensitivity of our assay to detect meaningful differences in PAK1 protein expression. Future studies are needed to evaluate whether alterations in PAK1 phosphorylation states, or alterations in protein expression of other members of the PAK family, are present in schizophrenia.
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影响因子：
4.8
作者：
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通讯作者：
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